The present studies in rats have demonstrated an important in vivo antitumor role for natural killer (NK) cells. A number of biological response modifiers (BRM) have been shown to augment the activity of these cells and thereby inhibit the establishment and growth of tumor cells in the lungs. To obtain additional evidence on the in vivo behavior of NK cells and to obtain data needed for the investigation of the possible immunotherapeutic use for T cells and large granular lymphocytes (LGL, the population known to mediate NK activity), adoptive transfer studies with chromium-51 and indium-111 labeled LGL and T cells were performed. The results demonstrate a distribution pattern which resembles the organ distribution for these cells, with a significant percentage of both LGL and T cells recovered from subcutaneous mammary tumors. In addition, the adoptive transfer of LGL into recipients with depressed NK activity was shown to restore in vitro tumor cell cytotoxicity, in vivo clearance of tumor cells from the lungs, and to inhibit the development of artificially induced lung metastases. These results provide the first direct evidence for an important in vivo role for NK cells and suggest that the adoptive transfer of highly enriched LGL populations should be further considered as one potential immunotherapeutic regimen in cancer patients.